Abstract
BackgroundLarge tumor suppressor (LATS) proteins are putative tumor suppressors and poorly expressed associated with poor outcome in many cancers. A recent immunohistochemistry study showed that LATS protein expression correlated with poor outcome in serous ovarian cancer.Materials and methodsWe analyzed LATS expression in various ovarian cancer transcriptomic data sets and immunohistochemically assessed LATS protein expression in a Swiss ovarian tumor cohort. Results were compared to clinicopathological characteristics and outcome. We also compared LATS protein expression in serous ovarian cancer cell lines to their EMT status (Western blotting) and drug sensitivity (MTT assay).ResultsThe analysis of 15 different transcriptomic data sets showed that LATS2 was associated with poorer outcome, while LATS1 was irrelevant (HR = 1.19 and HR = 1.00, respectively). The TCGA-RNASeqV2 data set showed that low LATS1 and LATS2 were associated with better survival in serous ovarian carcinoma. Despite heterogeneity among the different data sets, LATS expression is not an indicator of survival in serous ovarian cancer and LATS2 expression may even be tumorigenic. LATS expression was neither associated with survival nor with the stage and grade in the Swiss cohort. It was low in cystadenoma, intermediate in carcinoma, and high in borderline tumors and was higher in serous than mucinous ovarian carcinoma. LATS protein expression extent was comparable in epithelial-, intermediate-, and mesenchymal-type ovarian cancer cells and was not associated with drug sensitivity.ConclusionThese results are largely incompatible with a tumor-suppressive function of LATS in ovarian cancer, and LATS protein level is also not an indicator for drug sensitivity and EMT status of ovarian cancer cells.
Highlights
Large tumor suppressor (LATS) family proteins LATS1 and LATS2 have been proposed to be tumor suppressors
Neither LATS1 nor LATS2 expression was associated with favorable survival in ovarian cancer and LATS2 expression may even have a negative effect on survival
We investigated LATS expression in publicly accessible transcriptomic data sets and in tissue samples from a Swiss ovarian cancer patient cohort with regard to clinicopathological characteristics and outcome and based on the intriguing results determined in a panel of ovarian cancer cell lines whether LATS expression is an indicator for the Epithelial–mesenchymal transition (EMT) status of these cells and for drug sensitivity
Summary
Large tumor suppressor (LATS) family proteins LATS1 and LATS2 have been proposed to be tumor suppressors They have been reported to govern cellular homeostasis by preventing cell proliferation and migration, by inducing cell death and senescence, and by regulating cell cycle checkpoints to maintain genetic stability (Visser and Yang 2010; Furth and Aylon 2017). Conclusion These results are largely incompatible with a tumor-suppressive function of LATS in ovarian cancer, and LATS protein level is not an indicator for drug sensitivity and EMT status of ovarian cancer cells
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